Introduction

The 2015 Zika virus (ZIKV) outbreak in Brazil has led to global concern about the impact of the virus
and widespread fear of transmission beyond their borders. This essay aims to address the issues about
ZIKV that have arisen, including the background of the virus, the significance of understanding the
virus, and establishing an understanding of why ZIKV has had such a huge impact in Brazil.
ZIKV before Brazil
ZIKV is of the Flaviviridae family, which includes other flaviviruses such as dengue. It is transmitted
through an arthropod vector, thus is an arbovirus. ZIKV is an icosahedral enveloped virus, with a
positive-sense, single-stranded RNA genome that is non-segmented1. ZIKV manifests in fever, joint
swelling, rash and headaches in patients. Only 1 in 4 develop these symptoms. With the incubation
period taking up to 12 days, and the infection only lasting up to 7, ZIKV was considered a mild virus2.
Fig. 1: The 3.7 resolution cryoEM structure of ZIKV 3

The virus was first identified in Uganda in 1947. It was first discovered and isolated in humans in
Uganda and Tanzania in 1952. The earliest documented epidemics were in 2007, in the islands of Yap
and Gabon. Another outbreak was well-documented in French Polynesia in 2013-144. Before the 2015
outbreak in Brazil, the vectors by which ZIKV is transmitted were determined to be mosquitoes of the
Culicidae family and Aedes genus5. Not much concern was given to ZIKV before Brazil, and research
had not discovered any cause for worry, making the outbreak of ZIKV and the corresponding increase
of microcephaly cases in Brazil all the more surprising.

ZIKV and microcephaly

Microcephaly is an observed condition where the affected have a smaller brain than average for their
gender, age and race, with the head circumference equal to or more than 3 times of standard
deviation lesser6. The association of microcephaly with ZIKV could have emerged this late because
ZIKV has not impacted such a large population with no immunity before. Previously reported
outbreaks have only occurred in the isolated and small populations of island nations Yap and Gabon,
or in French Polynesia. An outbreak in a larger population would attract more scrutiny and research.
During the 2007 outbreak, no abnormal increase in microcephaly was reported. Brazil has however
seen an increase from 163 cases per year to 839 confirmed cases with 2000 more unconfirmed cases.
Research initiated in French Polynesia after the Brazilian outbreak found an increase of 17 cases in
20157.
What could explain the late discovery of the link might also be that ZIKV might have mutated during
the spread of the virus throughout the world 8. ZIKV would, only recently, have been able to cross over
the placenta to affect the foetus of infected mothers.
Now that an association is suspected, researchers are searching for irrefutable evidence that ZIKV does
indeed cause microcephaly.
Scientific evidence
The first sign that ZIKV could potentially lead to microcephaly was the finding of viral RNA copies of
the ZIKV genome in a foetal brain by reverse transcriptase-polymerase chain reaction (RT-PCR) in a
study conducted in late 2015 9. The detailed study found 6.5 10 viral RNA copies per mg of brain
tissue and sequenced the whole ZIKV RNA genome from the brain tissue. This sequence had 99.7%
similarity with the sequence found in a patient in French Polynesia. The study further reported that
the foetal brain had almost complete agyria and internal hydrocephalus of the lateral ventricles.
Findings of multifocal collections of filamentous, granular, and neuron-shaped calcifications along
with macrophages expressing HLA-DR were reported as well. Groups of enveloped structures with
a bright interior resembling the remains of replication complexes that are characteristic of
flaviviruses could also signify that ZIKV has replicated in the foetal brain and in doing so caused
microcephaly. This is strong evidence that ZIKV has a significant role in microcephaly observed in
foetuses. The presence of macrophages and calcifications resembling scarring could suggest a role
played by the immune system in causing microcephaly. Many pathogenic bacteria and viruses have
been known to cause autoimmune diseases through the production of foreign antigens that are similar
to self-antigens in the body, causing the immune system to attack certain organs mistakenly identified
as the foreign antigen. These could possibly explain the dire consequences of ZIKV on foetuses.
However, this study could be wildly inaccurate for the fact that its findings were based on a single
case. Every individual reacts to viruses and disease differently, and even though the findings of this
study seem to corroborate ZIKVs role in causing microcephaly, it could be an isolated case.
Another study has found a link between ZIKV and Guillain-Barr syndrome (GBS) and suggests that the
mechanism through which GBS is effected could help explain why microcephaly occurs10. It suggests
that gangliosides, glycolipids chiefly located in the nervous system, are similar to surface molecules
on ZIKV, which lead to autoimmune disease. This could help confirm the findings and hypotheses
above, but, as the authors have noted, the research is still in its infancy. It also does not support the
fact that even as microcephaly cases increase, a majority of pregnant women who are infected by ZIKV
do not give birth to new-borns affected by microcephaly.

There are other factors which could explain the sudden increase of microcephaly, chief of which is
that Brazil could have underreported its microcephaly cases before the ZIKV outbreak, and
overreported them after. The 150 microcephaly cases in 2014 out of 3 million live births in Brazil was
small to the 2,500 of 4 million live births in the US, according to the CDC epidemiologist Margaret
Honein11. Microcephaly is hard to diagnose, and might lead to misdiagnoses in Brazil, especially since
the panic over ZIKV has set in.
Conclusion
As the number of microcephaly cases in Brazil increase, finding the appropriate treatment for ZIKV is
of paramount importance. However, other factors cannot be ruled out, since, more often than not,
diseases are a complex result of the interplay between multiple factors.
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